Aim: Longitudinal tracking of transplanted cells in clinical and experimental setups is crucial for evaluating the efficiency of retinal cell replacement therapies. Materials & methods: Gold nanoparticle-labeled photoreceptor precursors were transplanted in the vitreous and subretinal space of rats and were longitudinally tracked for over a month using optical coherence tomography, computed tomography and fluorescence fundus imaging. Results: This multimodal imaging approach enabled high-resolution long-term tracking and estimation of cell survival in the retina and vitreous, while displaying no toxic effects on the cells or the retina. Conclusion: These observations highlight the applicability of using gold nanoparticle for retinal cell tracking in existing experimental settings and its translational potential for providing more efficient retinal cell therapy in humans.
We describe an imaging approach based on an optical setup made up of a miniature, lensless, minimally invasive endoscope scanning a sample and matching post processing techniques that enable enhanced imaging capabilities. The two main scopes of this article are that this approach enables imaging beyond highly scattering medium and increases the resolution and signal to noise levels reaching single cell imaging. Our approach has more advantages over ordinary endoscope setups and other imaging techniques. It is not mechanically limited by a lens, the stable but flexible fiber can acquire images over long time periods (unlike current imaging methods such as OCT etc.), and the imaging can be obtained at a certain working distance above the surface, without interference to the imaged object. Fast overlapping scans enlarge the region of interest, enhance signal to noise levels and can also accommodate post-processing, super-resolution algorithms. Here we present that due to the setup properties, the overlapping scans also lead to dramatic enhancement of non-scattered signal to scattered noise. This enables imaging through highly scattering medium. We discuss results obtained from in vitro investigation of weak signals of ARPE cells, rat retina, and scattered signals from polydimethylsiloxane (PDMS) microchannels filled with hemoglobin and covered by intralipids consequently mimicking blood capillaries and the epidermis of human skin. The development of minimally invasive procedures and methodologies for imaging through scattering medium such as tissues can vastly enhance biomedical diagnostic capabilities for imaging internal organs. We thereby propose that our method may be used for such tasks in vivo.
Background -
Tissue-integrated micro-electronic devices for neural stimulation hold a great potential in restoring the functionality of degenerated organs, specifically, retinal prostheses, which are aimed at vision restoration. The fabrication process of 3D polymer-metal devices with high resolution and a high aspect-ratio (AR) is very complex and faces many challenges that impair its functionality.
Approach -
Here we describe the optimization of the fabrication process of a bio-functionalized 3D high-resolution 1mm circular subretinal implant composed of SU-8 polymer integrated with dense gold microelectrodes (23µm pitch) passivated with 3D micro-well-like structures (20µm diameter, 3µm resolution). To this end, a nickel (Ni) evaporated silicon (Si) wafer was sequentially spin-coated with SU-8 and photolithographed layer-by-layer, with a sharp electrode formation achieved through a two-step bi-layer lift-off process using LOR/AZ, followed by Cr/Au thin-layer sputter deposition to increase the adhesion. Next, the device was released by overnight Ni wet-etching using nitric acid, after which it was bio-functionalized with N2 plasma treatment and the addition of the bio-adhesion molecule arginine-glycine-aspartic acid (RGD).
Main results - In-vitro
and in-vivo investigations, including SEM and FIB cross section examinations, revealed a good structural design, as well as a good integration of the device in the rat sub-retinal space and cell migration into the wells. The reported process and optimization steps described here in detail can aid in the design and fabrication of similar neural implants.
Conclusions -
The reported process and optimization steps described here in detail can aid in the design and fabrication of retinal prosthetic devices or similar neural implants.
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